45 results on '"Issei, Tokimatsu"'
Search Results
2. Successful Treatment of Breakthrough Trichosporon asahii Fungemia by the Combination Therapy of Fluconazole and Liposomal Amphotericin B in a Patient with Follicular Lymphoma
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Kazuhiro Itoh, Issei Tokimatsu, Hiroshi Tsutani, Hiromichi Iwasaki, Eiju Negoro, Takahiro Yamauchi, and Hiroko Shigemi
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0301 basic medicine ,medicine.medical_specialty ,Antifungal Agents ,Veterinary (miscellaneous) ,030106 microbiology ,Follicular lymphoma ,Trichosporon asahii ,Applied Microbiology and Biotechnology ,Microbiology ,Gastroenterology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Trichosporon ,Internal medicine ,Amphotericin B ,Trichosporonosis ,medicine ,Humans ,Blood culture ,Fluconazole ,Lymphoma, Follicular ,Fungemia ,Voriconazole ,medicine.diagnostic_test ,business.industry ,Basidiomycota ,Micafungin ,Middle Aged ,bacterial infections and mycoses ,medicine.disease ,business ,Agronomy and Crop Science ,medicine.drug - Abstract
Invasive trichosporonosis is a rare and lethal fungal infection that occurs in immunocompromised patients. Breakthrough trichosporonosis can occur in patients treated with echinocandins since Trichosporon spp. are resistant to these antifungal agents. We report a case of breakthrough Trichosporon asahii fungemia. A 62-year-old Japanese woman with relapsed follicular lymphoma was treated empirically with broad-spectrum antibiotics and micafungin due to an intermittent fever during reinduction chemotherapy. After four cycles of anti-cancer chemotherapy, she experienced a high neutropenic fever and T. asahii was subsequently detected from a blood culture. The patient was not given voriconazole due to the contraindication for use with carbamazepine, and she was successfully treated with fluconazole plus liposomal amphotericin B without any serious complications. The combined therapy of fluconazole and liposomal amphotericin B may therefore be useful in treating T. asahii fungemia, especially in patients receiving antiepileptic agents.
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- 2020
3. Combination treatment of short-course systemic corticosteroid and favipiravir in a successfully treated case of critically ill COVID-19 pneumonia with COPD
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Yoshio Watanabe, Shin Ohta, Tomoki Uno, Yoshito Miyata, Megumi Jinno, Hitoshi Ikeda, Haruna Sato, Yuiko Goto, Chisato Onitsuka, Issei Tokimatsu, Sojiro Kusumoto, Tomoyuki Kimura, Kuniaki Hirai, Tetsuya Homma, Yasunari Kishino, Tomoko Kawahara, Hiroki Sato, Shintaro Suzuki, Yoshitaka Uchida, Yoko Sato, Hatsuko Mikuni, Mayumi Yamamoto, Hideki Inoue, Hironori Sagara, and Akihiko Tanaka
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Case Report ,Favipiravir ,Gastroenterology ,MERS, middle east respiratory syndrome ,03 medical and health sciences ,SRAS-CoV-2, severe acute respiratory syndrome coronavirus 2 ,0302 clinical medicine ,PCR, polymerase chain reaction ,Internal medicine ,medicine ,COPD ,SFTSV, severe fever with thrombocytopenia syndrome virus ,ARDS, acute respiratory distress syndrome ,COVID-19, coronavirus disease 2019 ,Mechanical ventilation ,lcsh:RC705-779 ,Systemic corticosteroid ,business.industry ,SARS-CoV-2 ,GOLD, The Global Initiative for Chronic Obstructive Lung Disease ,COVID-19 ,Pneumonia ,lcsh:Diseases of the respiratory system ,SpO2, peripheral capillary oxygen saturation ,medicine.disease ,ICU, intensive care unit ,CT, computed tomography ,respiratory tract diseases ,030228 respiratory system ,Respiratory failure ,COPD, chronic obstructive pulmonary disease ,030220 oncology & carcinogenesis ,Prednisolone ,CRP, C-reactive protein ,Middle East respiratory syndrome ,Corticosteroid ,RSV, respiratory syncytial virus ,business ,medicine.drug ,WBC, white blood cell - Abstract
Use of systemic corticosteroids for the treatment for coronavirus disease 2019 (COVID-19) among chronic obstructive pulmonary disease (COPD) patients is not well described. A 58-year-old man with fever and progressive dyspnea was admitted to the Showa University Hospital, and showed severe respiratory failure which needed mechanical ventilation. His chest computed tomography scanning showed emphysema and bilateral ground-glass opacity caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. He received 30 mg prednisolone for five days with antiviral drug of favipiravir, and was successfully extubated on day five. A SARS-CoV-2 polymerase chain reaction (PCR) test became negative on day 15. He was discharged on day 21. Serum IgM and IgG antibodies against SARS-CoV-2 converted to positive on day 7 and they kept positive on day 54 for both IgM and IgG. Combination treatment of short-course systemic corticosteroid and favipiravir might improve the prognosis for critically ill COVID-19 pneumonia with COPD without negative influence on viral clearance or antibody production.
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- 2020
4. Invasive Scopulariopsis alboflavescens infection in patient with acute myeloid leukemia
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Rina Sakai, Kei Takenaka, Sho Nishimura, Mitsuhiro Ito, Yu Mizutani, Katsuya Yamamoto, Seiji Kakiuchi, Kimikazu Yakushijin, Katsuhiko Kamei, Shinichiro Kawamoto, Keiji Kurata, Yoshiharu Miyata, Akihito Kitao, Hironobu Minami, Issei Tokimatsu, Hiroya Ichikawa, and Hiroshi Matsuoka
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0301 basic medicine ,medicine.medical_specialty ,Combination therapy ,medicine.medical_treatment ,030106 microbiology ,Hematopoietic stem cell transplantation ,Immunocompromised Host ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Voriconazole ,Hematology ,biology ,business.industry ,Myeloid leukemia ,Pneumonia ,medicine.disease ,biology.organism_classification ,Dermatology ,Leukemia, Myeloid, Acute ,Mycoses ,Scopulariopsis ,Female ,Scopulariopsis alboflavescens ,business ,medicine.drug - Abstract
Scopulariopsis alboflavescens is a soil saprophyte that is widely distributed in nature. Recently, there have been increasing number of reports of invasive infections with Scopulariopsis species in immunocompromised patients. In this report, we described an adult woman with acute myeloid leukemia and who developed S. alboflavescens pneumonia. Liposomal amphotericin B and voriconazole combination therapy was unsuccessful and the patient died because of pneumonia. Scopulariopsis is highly resistant to available antifungal agents and almost invariably fatal. This case report should alert clinicians to the importance of listing Scopulariopsis as a pathogenic fungus in immunocompromised patients.
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- 2018
5. A New Amino Acid Substitution at G150S in Lanosterol 14-α Demethylase (Erg11 protein) in Multi-azole-resistant Trichosporon asahii
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Hiroshi Ishii, Kentaro Watanabe, Issei Tokimatsu, Hisako Kushima, Rie Kawano, and Jun-ichi Kadota
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0301 basic medicine ,chemistry.chemical_classification ,Itraconazole ,Lanosterol ,Point mutation ,030106 microbiology ,Fungal genetics ,Trichosporon asahii ,Microbiology ,Amino acid ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Infectious Diseases ,chemistry ,medicine ,Azole ,Fluconazole ,medicine.drug - Abstract
The mechanisms of azole resistance in Trichosporon asahii have not yet been fully clarified. We previously showed that T. asahii has the ERG11 gene, coding lanosterol 14-α-demethylase (Erg11 protein; Erg11p), which is the primary target of azoles. A single amino acid substitution at G453R in Erg11p was found to induce changes in the affinity of this enzyme for azoles, especially fluconazole, in vitro. In the present study, we investigated the DNA sequences of the ERG11 gene using six different strains of clinically isolated T. asahii that were highly resistant to multi-azoles, including fluconazole, itraconazole, and voriconazole. All of the T. asahii strains had a point mutation (G448A) that caused a single amino acid substitution at G150S in Erg11p. This amino acid is highly conserved among major fungal pathogens. We identified a new point mutation in the ERG11 gene that is common to clinically isolated azole-resistant T. asahii strains, suggesting that this mutation is associated with the multi-azole resistance of T. asahii.
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- 2017
6. A Prospective Study of the Efficacy, Safety and Pharmacokinetics of Enteral Moxifloxacin in the Treatment of Hemodialysis Patients with Pneumonia
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Katsumi Shigemura, Hiroki Yoshikawa, Tadashi Tomo, Masato Fujisawa, Issei Tokimatsu, Jun-ichi Kadota, Soichi Arakawa, Fukashi Yamamichi, and Tomohiro Kotaki
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0301 basic medicine ,Male ,medicine.medical_specialty ,030106 microbiology ,Population ,Cmax ,Administration, Oral ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Anti-Infective Agents ,Levofloxacin ,Moxifloxacin ,Renal Dialysis ,Internal medicine ,Internal Medicine ,medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,education ,Intensive care medicine ,Adverse effect ,Aged ,education.field_of_study ,hemodialysis ,business.industry ,General Medicine ,Pneumonia ,Middle Aged ,medicine.disease ,Anti-Bacterial Agents ,Community-Acquired Infections ,Ceftriaxone ,Kidney Failure, Chronic ,Original Article ,Female ,moxifloxacin ,business ,pharmacokinetics ,medicine.drug ,Fluoroquinolones - Abstract
Objectives To investigate the efficacy of oral moxifloxacin (MFLX) as a treatment for pneumonia in hemodialysis (HD) patients and the pharmacokinetic (PK) profile of MFLX after oral administration. Methods Thirteen adult patients who required HD due to chronic renal failure were enrolled in the present study, which was performed to investigate the treatment of community-acquired pneumonia in HD patients. A standard dose of MFLX (400 mg, once daily) was administered. The therapy was continued, discontinued, or switched to another antibiotic depending on the response of the pneumonia to MFLX. A population PK model was developed using the post-hoc method. Results In total, 13 HD patients with pneumonia (male, n=7; female, n=6) were enrolled in the present study. The evaluation on the 3rd day showed that treatment was successful in 11 patients (84.6%) and that 10 patients were cured (76.9%). In the one case in which MFLX treatment failed, the patient was cured by switching to ceftriaxone (CTRX) (2 g, intravenously) plus levofloxacin (LVFX) (250 mg, orally). The causative bacterium in this male patient was P. aeruginosa. It did not display resistance to fluoroquinolones. One patient had liver dysfunction due to MFLX. The estimated PK parameters of MFLX were as follows: AUC0→24, 61.04±17.74 μg h/mL; Cmax, 5.25±1.12 μg/mL; and Ctrough, 1.15±0.45 μg/mL. The PK parameters of MFLX among the patients in whom adverse events occurred or in whom a cure was not achieved did not differ from those of the other patients to a statistically significant extent. Conclusion MFLX showed good efficacy and safety in HD patients with community-acquired pneumonia and the results of the PK analysis were favorable. Further prospective studies with larger numbers of patients will be needed to draw definitive conclusions.
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- 2017
7. Monitoring quinolone resistance due to Haemophilus influenzae mutations (2012–17)
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Takahiro Takuma, Yoshihito Niki, Issei Tokimatsu, Yasuhiro Nagatomo, Kunihiko Fukuchi, and Tetsuro Shirakura
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Sitafloxacin ,biology ,Chemistry ,Topoisomerase IV ,medicine.drug_class ,Broth microdilution ,medicine.disease_cause ,Quinolone ,DNA gyrase ,Haemophilus influenzae ,Microbiology ,Penicillin ,Moxifloxacin ,medicine ,biology.protein ,medicine.drug - Abstract
Among drug-resistant bacteria of recent concern, we determined minimum inhibitory concentrations (MICs) of six different quinolone antibacterial agents in Haemophilus influenzae and performed molecular genetic analysis in addition to the exploration for β-lactamase-producing and β-lactamase negative ampicillin-resistant H. influenzae (BLNAR). A total of 144 clinical H. influenzae strains isolated at the Showa University Hospital between 2012 and 2017 were subjected to MIC determination for penicillin/quinolone antibacterial agents using the nitrocefin method and the Clinical and Laboratory Standards Institute broth microdilution method. Moreover, amino acid mutations in the quinolone resistance-determining regions (QRDRs) were analyzed in the isolates showing MIC value of ≥ 0.25 µg/ml of quinolone antibacterial agents. Increasing proportions of BLNAR were noted, with 15% in 2015 to 43.5% in 2016 and 63.6% in 2017. Among quinolone antibacterial agents, all isolates remained susceptible to sitafloxacin (STFX), and STFX showed strong inhibitory potencies against both DNA gyrase and topoisomerase IV. For moxifloxacin (MXF), however, strains with MIC value of 0.5 µg/ml were detected every year since 2013 except 2015. Amino acid mutations were investigated in 17 isolates (11.8%) with MXF MIC value of ≥0.25 µg/ml, and confirmed in 11 isolates (7.6%), of which mutations of GyrA were found in 9 isolates. Future antibacterial drug regimens may need to address the emergence of quinolone-resistant H. influenzae.
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- 2019
8. Selection of Oral Antifungals for Initial Maintenance Therapy in Chronic Pulmonary Aspergillosis: A Longitudinal Analysis
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Kenji Ogawa, Yoshifumi Imamura, Satoru Fujiuchi, Hiroshi Mukae, Takahiro Takazono, Issei Tokimatsu, Kazuko Yamamoto, Katsunori Yanagihara, Shigeru Kohno, Yuta Hayashi, Hiroshi Kakeya, Kiyoshi Ichihara, Taiga Miyazaki, Kazuma Kishi, Yoshitsugu Miyazaki, Tomomi Saijo, Tsunehiro Ando, Koichi Izumikawa, and Masato Tashiro
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0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Antifungal Agents ,Maintenance ,Itraconazole ,030106 microbiology ,03 medical and health sciences ,0302 clinical medicine ,Maintenance therapy ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Risk factor ,Aged ,Retrospective Studies ,Voriconazole ,business.industry ,Chronic pulmonary aspergillosis ,Odds ratio ,medicine.disease ,Confidence interval ,Clinical trial ,Infectious Diseases ,Pulmonary Aspergillosis ,business ,Follow-Up Studies ,medicine.drug - Abstract
Background There are limited data for direct comparisons of the efficacy of oral itraconazole (ITCZ) and oral voriconazole (VRCZ) therapy in the treatment of chronic pulmonary aspergillosis (CPA). Methods We conducted a retrospective, follow-up, observational study of CPA patients enrolled in 2 previous multicenter trials. Results Of the 273 CPA patients, 59 and 101 patients started maintenance therapy with oral ITCZ and oral VRCZ, respectively, just after the end of acute intravenous therapy in each trial. At the end of the observation period in this follow-up study (median observation period, 731 days), the percentage of patients who showed improvement was lower in the ITCZ group than in the VRCZ group (18.2% vs 40.0%). However, after including stable patients, the percentages were 50.9% and 52.6%, respectively, in the ITCZ and VRCZ groups, which were not significantly different (P = .652). Multivariable Cox regression analysis showed no significant influence of the choice of initial maintenance treatment (ITCZ or VRCZ) on overall mortality as well as CPA-associated mortality. Multivariable logistic regression showed that oral ITCZ selection for initial maintenance therapy was an independent risk factor for hospital readmission and switching to other antifungal agents (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.3–7.5 and OR, 5.7; 95% CI, 2.0–15.7, respectively). Conclusions Oral VRCZ for initial maintenance therapy showed better effectiveness than oral ITCZ for clinical improvement in CPA patients. There was no difference in crude mortality between initial maintenance therapy with VRCZ and ITCZ, especially in elderly CPA patients.
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- 2019
9. Effects of Sulfamethoxazole-Trimethoprim on Airway Colonization with Pneumocystis jirovecii
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Kenji Umeki, Hiroshi Ishii, Takako Sato, Jun-ichi Kadota, Issei Tokimatsu, and Hisako Kushima
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Microbiology (medical) ,medicine.medical_specialty ,Pneumocystis pneumonia ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Medicine ,Pneumocystis jirovecii ,030212 general & internal medicine ,Sulfamethoxazole/Trimethoprim ,030203 arthritis & rheumatology ,medicine.diagnostic_test ,biology ,business.industry ,General Medicine ,medicine.disease ,biology.organism_classification ,Trimethoprim ,respiratory tract diseases ,Pneumonia ,Infectious Diseases ,Bronchoalveolar lavage ,chemistry ,Immunology ,Sputum ,medicine.symptom ,business ,Airway ,medicine.drug - Abstract
Reactivation of latent infection is considered to be the main mechanism underlying the development of Pneumocystis pneumonia in immunosuppressed patients. We retrospectively assessed the effects of prophylactic administration of sulfamethoxazole-trimethoprim on the development of P. pneumonia and airway colonization with P. jirovecii in patients undergoing examinations to diagnose or rule out P. pneumonia. Polymerase chain reaction was performed to detect P. jirovecii in bronchoalveolar lavage fluid or sputum of 60 consecutive patients between 2004 and 2012. No patients who received the prophylactic administration of sulfamethoxazole-trimethoprim (n = 10) developed P. pneumonia or demonstrated airway colonization with P. jirovecii, and none of the patients who developed P. pneumonia (n = 11) or showed colonization (n = 9) had received prophylactic treatment. Furthermore, 20 (40%) of 50 patients without prophylactic treatment showed positive results on the P. jirovecii DNA polymerase chain reaction, but all 10 patients who had prophylactic treatment showed negative results (Fisher's exact test, P = 0.02). Therefore, the prophylactic administration of sulfamethoxazole-trimethoprim has potential to be effective in preventing P. pneumonia as well as eliminating airway colonization with P. jirovecii. Further studies targeting large cohorts of patients with a variety of underlying diseases are required to develop recommendations regarding the prophylactic administration of sulfamethoxazole-trimethoprim.
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- 2016
10. [The Deveroppment of Screening Methods Using the Disk Diffusion Method for Carbapenemase-producing Enterobacteriaceae]
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Jun Saegusa, Saori Kobayashi, Tatsuya Nakamura, Soichi Arakawa, Go Oji, Issei Tokimatsu, Kenichiro Onuma, Mari Kusuki, and Nobuhide Hayashi
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0301 basic medicine ,Veterinary medicine ,Carbapenem ,Imipenem ,biology ,Panipenem ,030106 microbiology ,Faropenem ,General Medicine ,Microbial Sensitivity Tests ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Enterobacteriaceae ,Meropenem ,beta-Lactamases ,Diffusion ,03 medical and health sciences ,chemistry.chemical_compound ,Carbapenem-Resistant Enterobacteriaceae ,chemistry ,Bacterial Proteins ,medicine ,Doripenem ,Biapenem ,medicine.drug - Abstract
Carbapenem-resistant Enterobacteriaceae (CRE) are increasing globally. Particularly, carbapenemase-producing Enterobacteriaceae (CPE) are of concern. Rapid and accurate detection of these strains is critical for appropriate antimicrobial use and hospital infection control. In the present study, criteria for CPE screening were examined using a carbapenem susceptibility disk. Carbapenemase producers showed minimal inhibition zones for faropenem (5 μg): 6-12 mm (mean: 6.9 mm). Some strains with the IMP-6 genotype showed inhibition zones of >30 mm for imipenem (10 μg) and biapenem (10 μg). All strains that formed inhibition zones for FRPM had the IMP-6 genotype. The cut off values of carbapenemase-producers, determined by ROC analysis, were 12 mm for FRPM, 24 mm for meropenem (10 μg), 29 mm for BIPM, 25 mm for doripenem (10 μg), 26 mm for IPM, and 24 mm for panipenem (10 μg). Thus, the sensitivity was the highest (100%) for FRPM. Specificities were 93.44% for MEPM and DRPM and 85.25% for FRPM. Consequently, a drug sensitivity test using FRPM (5 μg) disks facilitates simple and accurate CPE screening.
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- 2018
11. The development of diffuse panbronchiolitis during the treatment with long-term, low-dose clarithromycin for chronic sinusitis
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Yuko Usagawa, Tomoko Ono, Issei Tokimatsu, Masaru Ando, Hiroki Yoshikawa, Takashi Hirano, and Jun-ichi Kadota
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0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,Haemophilus Infections ,030106 microbiology ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Clarithromycin ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,In patient ,030212 general & internal medicine ,Sinusitis ,business.industry ,Low dose ,Chronic sinusitis ,medicine.disease ,Anti-Bacterial Agents ,Chronic cough ,Infectious Diseases ,Chronic Disease ,Copious sputum ,Bronchiolitis ,medicine.symptom ,business ,Diffuse panbronchiolitis ,medicine.drug - Abstract
Diffuse panbronchiolitis (DPB) is a progressive inflammatory airway disease characterized by a chronic cough, copious sputum expectation, dyspnea, and chronic sinusitis. Owing to the long-term treatment of low-dose macrolides, the prognosis has been remarkably improved. However, in some cases, patients are refractory to macrolides, and the subsequent treatment strategies are controversial. We herein present a patient with the onset of DPB during treatment with long-term, low-dose clarithromycin (CAM) for chronic sinusitis who was successfully treated by switching to long-term treatment with normal-dose CAM. We should recognize that DPB may develop in patients with chronic sinusitis despite treatment with a long-term, low-dose macrolide. We also propose that increasing the dose of macrolide may be a useful strategy for treating refractory patients.
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- 2018
12. Molecular epidemiologic study of Clostridium difficile infections in university hospitals: Results of a nationwide study in Japan
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Masato Fujisawa, Noriko Nakanishi, Soichi Arakawa, Hiroyuki Yoshida, Koichi Kitagawa, Shinya Kinugawa, Kayo Osawa, Katsumi Shigemura, and Issei Tokimatsu
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0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,030106 microbiology ,Clostridium difficile toxin A ,Microbial Sensitivity Tests ,medicine.disease_cause ,Polymerase Chain Reaction ,Ribotyping ,Severity of Illness Index ,Microbiology ,Hospitals, University ,03 medical and health sciences ,Feces ,Inhibitory Concentration 50 ,Young Adult ,Bacterial Proteins ,Japan ,Vancomycin ,Metronidazole ,Epidemiology ,medicine ,Humans ,Pharmacology (medical) ,Aged ,ADP Ribose Transferases ,Aged, 80 and over ,Pore-forming toxin ,Molecular Epidemiology ,business.industry ,Toxin ,Clostridioides difficile ,Clostridium difficile ,Middle Aged ,Antimicrobial ,Anti-Bacterial Agents ,Infectious Diseases ,Epidemiological Monitoring ,Clostridium Infections ,Female ,business ,medicine.drug - Abstract
We conducted a nationwide molecular epidemiological study of Clostridium difficile infection (CDI) in Japan investigated the correlation between the presence of binary toxin genes and CDI severity. This is the first report on molecular epidemiological analyses for CDI in multiple university hospitals in Japan, to our knowledge. We examined 124,484 hospitalized patients in 25 national and public university hospitals in Japan between December 2013 and March 2014, investigating antimicrobial susceptibilities and toxin-related genes for C. difficile isolates from stools. Epidemiological genetic typing was performed by PCR-ribotyping and repetitive sequence-based (rep)-PCR to examine the genetic similarities. The results detected toxin A-positive, toxin B-positive, binary toxin-negative (A+B+CDT−) detected from 135 isolates (80.8%) and toxin A-negative, toxin B-positive, binary toxin-negative (A− B+CDT−) in 23 (13.8%). Toxin A-positive, toxin B-positive, and binary toxin-positive (A+B+CDT+) were seen in 9 isolates (5.4%). Vancomycin (n = 81, 37.7%) or metronidazole (n = 88, 40.9%) therapies were undertaken in analyzed cases. Ribotypes detected from isolates were 017/subgroup 1, 070, 078, 126, 176, 449, 475/subgroup 1, 499, 451, 566 and newtypes. Rep-PCR classified 167 isolates into 28 cluster groups including 2–15 isolates. In addition, 2 pairs of strains isolated from different institutions belonged to the same clusters. Seven out of 9 (77.8%) of the patients with binary toxin producing strains had “mild to moderate” outcome in evaluated symptoms. In conclusion, we found that binary toxin did not show regional specificity and had no relevance to severity of CDI.
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- 2018
13. Association of overexpression of efflux pump genes with antibiotic resistance in Pseudomonas aeruginosa strains clinically isolated from urinary tract infection patients
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Katsumi Shigemura, Ayaka Kato, Toshiro Shirakawa, Kayo Osawa, Soichi Arakawa, Issei Tokimatsu, and Masato Fujisawa
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Male ,medicine.drug_class ,Antibiotics ,Drug resistance ,Biology ,medicine.disease_cause ,Bacterial genetics ,Microbiology ,Antibiotic resistance ,Risk Factors ,Levofloxacin ,Drug Resistance, Bacterial ,Drug Discovery ,medicine ,Humans ,Pseudomonas Infections ,Aged ,Aged, 80 and over ,Pharmacology ,Reverse Transcriptase Polymerase Chain Reaction ,Pseudomonas aeruginosa ,Gene Expression Regulation, Bacterial ,Odds ratio ,Middle Aged ,Anti-Bacterial Agents ,RNA, Bacterial ,Genes, Bacterial ,Multivariate Analysis ,Urinary Tract Infections ,Female ,Efflux ,Genes, MDR ,medicine.drug - Abstract
There are several mechanisms for antibiotic-resistant Pseudomonas aeruginosa. The purpose of this study is to investigate the association between the expression of efflux pump-coding genes and antibiotic resistance in P. aeruginosa causing urinary tract infections (UTIs). We extracted the RNA from 105 clinical strains of P. aeruginosa isolated from UTI patients with full data on antibiotic MICs and assayed real-time quantitative reverse-transcription PCR. We investigated the gene expressions of four resistance nodulation cell division-type multi-drug efflux pump systems (MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY(-OprA)) and the correlation of the MICs of nine antibiotics, risk factors and antibiotic resistance-related genes with expressions of mexB, mexC, mexE and mexY. Multivariate statistical data demonstrated a significant relationship between increased expression of mexB or mexC and complicated UTI (Odds ratio=8.03, P
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- 2015
14. Antifungal susceptibility and drug-resistant mechanism of Trichosporon
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Jun-ichi Kadota, Hiroshi Ishii, Hisako Kushima, and Issei Tokimatsu
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chemistry.chemical_classification ,Drug ,biology ,business.industry ,media_common.quotation_subject ,Drug resistance ,Trichosporon asahii ,biology.organism_classification ,Trichosporonosis ,medicine.disease ,Microbiology ,Minimum inhibitory concentration ,Infectious Diseases ,chemistry ,Trichosporon ,Medicine ,Azole ,business ,Fluconazole ,medicine.drug ,media_common - Abstract
Most cases of deep-seated trichosporonosis develop in patients with neutropenia, but it has recently been reported that breakthrough infections with Trichosporon species can develop during the use of candin family of antifungal agents. This is due to the primary resistance of the causal fungus, Trichosporon asahii (T. asahii), to the candin agents. On the other hand, there has been a case report of infection with Trichosporon that presented high-level resistance to the azole family of antifungal agents. Therefore, the possibility that the frequent use of azole agents may lead to secondary resistance to these agents is a cause for concern. Since trichosporonosis is a relatively rare infectious disease, there has been no established breakpoint for this fungus to various antifungal agents, wherein we cannot precisely confirm its sensitivity or resistance to the agents. However, our experiment demonstrated one of the processes for acquired drug resistance, wherein the minimal inhibitory concentration of fluconazole for T. asahii was markedly elevated after its long-term in vitro exposure to the drug. Although the mechanisms for drug-resistance of Trichosporon species are unknown, it is supposed that they are the same as the mechanisms found in Candida and Aspergillus species, namely, modification of target molecules or decrease of access to the molecules. Since cases of trichosporonosis are likely to increase in the future, we believe that there is an urgent need to establish the breakpoint for T. asahii based on large-scale drug sensitivity tests, as well as to elucidate its drug-resistance mechanisms.
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- 2015
15. Comparison of antibiotics use, urinary tract infection (UTI)-causative bacteria and their antibiotic susceptibilities among 4 hospitals with different backgrounds and regions in Japan
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Issei Tokimatsu, Katsumi Shigemura, Koichi Kitagawa, Kayo Osawa, Fukashi Yamamichi, Kei Takaba, Masato Fujisawa, and Masashi Nomi
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0301 basic medicine ,medicine.medical_specialty ,medicine.drug_class ,030106 microbiology ,Antibiotics ,Cefazolin ,Microbial Sensitivity Tests ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Antibiotic resistance ,Japan ,Levofloxacin ,Internal medicine ,Ampicillin ,Drug Resistance, Bacterial ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Urinary tract infection (UTI) ,Pharmacology ,biology ,business.industry ,Drug Resistance, Microbial ,Bacterial Infections ,medicine.disease ,biology.organism_classification ,Anti-Bacterial Agents ,Infectious Diseases ,Oncology ,Urinary Tract Infections ,business ,Bacteria ,medicine.drug ,Piperacillin - Abstract
In this study, we compared the antibiotic use, urinary tract infection-causative bacteria and their antibiotic susceptibilities among four hospitals with different backgrounds and regions in Japan in 2014. Frequency of antibiotic use (antibiotic use density: AUD/all AUD) were: ampicillin: 0.21-20.3 (median: 1.6) and cefazolin: 0.8-34.2 (2.5), representatively. The antibiotic resistant rates of Escherichia coli were ampicillin: 1.1-52.3% (median: 51.8%), piperacillin: 47.9-49.1% (48.0%), cefazolin: 23.2-34.1% (28.9%), levofloxacin: 36.6-43.8% (40.2%).We found that there were significant correlations (1) between antibiotic resistance of E. coli and annual total amount of antibiotic use (p = 0.017), annual number of days of antibiotic use (p = 0.002) and days of therapy (DOT, p = 0.002), and (2) between antibiotic resistance of extended-spectrum β-lactamase-producing bacteria and annual number of days of antibiotic use (p = 0.004) and DOT (p = 0.004) in a rehabilitation hospital. These results suggested that more antibiotic uses could lead to antibiotic resistances. Further analyses with more number of data are being undertaken.
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- 2017
16. Long-term efficacy of comprehensive multidisciplinary antibiotic stewardship programs centered on weekly prospective audit and feedback
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Issei Tokimatsu, Mari Kusuki, Takeshi Ioroi, Ikuko Yano, Kazuhiko Yamashita, Tatsuya Nishioka, Tomoyuki Sakaue, Atsushi Uda, Midori Hirai, Kei Ebisawa, Manabu Nagata, Akira Mukai, Tatsuya Nakamura, Goh Ohji, Sho Nishimura, Yasuhisa Abe, Hiroyuki Yoshida, Chihiro Koike, Takeshi Kimura, Kentaro Iwata, and Soichi Arakawa
- Subjects
0301 basic medicine ,Microbiology (medical) ,Methicillin-Resistant Staphylococcus aureus ,medicine.medical_specialty ,medicine.drug_class ,Commission on Professional and Hospital Activities ,030106 microbiology ,Antibiotics ,Prospective audit and feedback ,medicine.disease_cause ,Feedback ,03 medical and health sciences ,Antimicrobial Stewardship ,0302 clinical medicine ,Japan ,Levofloxacin ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Intensive care medicine ,Long-term efficacy ,Antibiotic stewardship ,Clostridiales ,business.industry ,Pseudomonas aeruginosa ,Prospective audit ,Incidence (epidemiology) ,General Medicine ,Bacterial Infections ,medicine.disease ,Infectious Diseases ,Treatment Outcome ,Staphylococcus aureus ,Controlled Before-After Studies ,Bacteremia ,Antibiotic Stewardship ,Interdisciplinary Communication ,Multidisciplinary collaboration ,business ,medicine.drug - Abstract
Objective: To evaluate the long-term effects of comprehensive antibiotic stewardship programs (ASPs) on antibiotic use, antimicrobial-resistant bacteria, and clinical outcomes. Design: Before-after study. Setting: National university hospital with 934 beds. Intervention: Implementation in March 2010 of a comprehensive ASPs including, among other strategies, weekly prospective audit and feedback with multidisciplinary collaboration. Methods: The primary outcome was the use of antipseudomonal antibiotics as measured by the monthly mean days of therapy per 1000 patient days each year. Secondary outcomes included overall antibiotic use and that of each antibiotic class, susceptibility of Pseudomonas aeruginosa, the proportion of patients isolated methicillin-resistant Staphylococcus aureus (MRSA) among all patients isolated S. aureus, the incidence of MRSA, and the 30-day mortality attributable to bacteremia. Results: The mean monthly use of antipseudomonal antibiotics significantly decreased in 2011 and after as compared with 2009. Susceptibility to levofloxacin was significantly increased from 2009 to 2016 (P = 0.01 for trend). Its susceptibility to other antibiotics remained over 84% and did not change significantly during the study period. The proportion of patients isolated MRSA and the incidence of MRSA decreased significantly from 2009 to 2016 (P < 0.001 and = 0.02 for trend, respectively). There were no significant changes in the 30-day mortality attributable to bacteremia during the study period (P = 0.57 for trend). Conclusion The comprehensive ASPs had long-term efficacy for reducing the use of the targeted broad-spectrum antibiotics, maintaining the antibiotic susceptibility of P. aeruginosa, and decreasing the prevalence of MRSA, without adversely affecting clinical outcome.
- Published
- 2017
17. Risk factors for death from Stenotrophomonas maltophilia bacteremia
- Author
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Katsumi Shigemura, Koichi Kitagawa, Masato Fujisawa, Kayo Osawa, and Issei Tokimatsu
- Subjects
0301 basic medicine ,Male ,Carbapenem ,Stenotrophomonas maltophilia ,Antibiotics ,0302 clinical medicine ,Japan ,Risk Factors ,Pharmacology (medical) ,030212 general & internal medicine ,Hospital Mortality ,Prospective Studies ,Survivors ,Stenotrophomonas maltophilia bacteremia ,Prospective cohort study ,Child ,Aged, 80 and over ,biology ,Middle Aged ,Antimicrobial ,Anti-Bacterial Agents ,Hospitalization ,Intensive Care Units ,Infectious Diseases ,Child, Preschool ,Female ,medicine.symptom ,medicine.drug ,Microbiology (medical) ,Adult ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,030106 microbiology ,Microbial Sensitivity Tests ,03 medical and health sciences ,Young Adult ,Internal medicine ,Drug Resistance, Bacterial ,medicine ,Humans ,Aged ,Retrospective Studies ,business.industry ,Infant, Newborn ,Infant ,bacterial infections and mycoses ,medicine.disease ,biology.organism_classification ,Respiration, Artificial ,Bacteremia ,Sputum ,business ,Gram-Negative Bacterial Infections - Abstract
Stenotrophomonas maltophilia has low pathogenicity potential, but if it causes bacteremia it can be fatal, because it has shown high resistance to many antibiotics and can be difficult to treat. Patient death from S. maltophilia bacteremia has increased since 2014 in our hospital. In this study, we investigated risk factors for death due to S. maltophilia bacteremia.Seventy patients from the hospital database with S. maltophilia bacteremia between January 2010 and July 2017 were investigated. We retrospectively analyzed risk factors including gender, age, wards, hospitalized duration, clinical history, devices, source of S. maltophilia identification, polymicrobial bacteremia, prior antimicrobial therapy, antimicrobial therapy after bacteremia, and resistance to antibiotics. The statistical analysis was performed to compare the period from 2010 to 2013 to from 2014 to 2017.Comparing the 2010-2013 period to the 2014-2017 period, it revealed that history of hospitalization, identification of S. maltophilia from sputum, polymicrobial bacteremia, prior carbapenem use, and mortality was significantly different in S. maltophilia bacteremia (p = 0.028, p = 0.004, p 0.001, p = 0.034, and p = 0.007, respectively). Comparison between non-survivors and survivors for 2010-2013 and 2014-2017 found ICU admission and ventilator use were seen more often in non-survivors (p = 0.030 vs p = 0.013 and p = 0.027 vs p = 0.010, respectively).Our analyses showed increase in mortality from S. maltophilia bacteremia from 2014 to 2017, and that non-survivors had a higher frequency of ICU admission and ventilator use in both the 2010-2013 and 2014-2017 periods. There were more combination antimicrobial therapy cases after bacteremia in 2014-2017. Further prospective studies with larger numbers of patients should be undertaken for definitive conclusions.
- Published
- 2017
18. Efficacy and safety of levofloxacin in patients with bacterial pneumonia evaluated according to the new 'Clinical Evaluation Methods for New Antimicrobial Agents to Treat Respiratory Infections (Second Version)'
- Author
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Hiroshi Kakeya, Katsunori Yanagihara, Toshinori Kawanami, Hiroshi Mukae, Shigeru Kohno, Yoshihiro Yamamoto, Issei Tokimatsu, Kazuhiro Yatera, and Jun-ichi Kadota
- Subjects
Male ,Microbiology (medical) ,medicine.medical_specialty ,Levofloxacin ,Microbial Sensitivity Tests ,medicine.disease_cause ,Haemophilus influenzae ,Moraxella catarrhalis ,Anti-Infective Agents ,Japan ,Community-acquired pneumonia ,Internal medicine ,Streptococcus pneumoniae ,Pneumonia, Bacterial ,medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,Aged ,Aged, 80 and over ,biology ,business.industry ,Bacterial pneumonia ,Middle Aged ,medicine.disease ,Antimicrobial ,biology.organism_classification ,Surgery ,Pneumonia ,Infectious Diseases ,Female ,business ,medicine.drug - Abstract
The guideline for the "Clinical Evaluation Methods for New Antimicrobial Agents to Treat Respiratory Infections (Second Version)," published by the Japanese Society of Chemotherapy in January 2012, was proposed to achieve consistency with FDA guidelines based on the concept of clinical evaluation used in Japan. We assessed the clinical efficacy of levofloxacin (LVFX) in patients with bacterial pneumonia according to this new set of guidelines for the first time. The clinical efficacy of LVFX in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) at the test of cure (TOC) was 87.5% (56/64) and 85.7% (6/7), respectively, with an overall efficacy of 87.3% (62/71). The clinical efficacy of LVFX at TOC was as follows: intravenous 81.5% (22/27), oral 88.9% (24/27), switchover from intravenous to oral administration 100% (10/10), respectively. The bacterial eradication rate in the patients with CAP and HCAP and overall efficacy at the end of therapy (EOT) was 95.3% (41/43), 100.0% (4/4) and 95.7% (45/47), respectively. The frequent causative bacterial strains included Streptococcus pneumoniae (18), Haemophilus influenzae (14) and Moraxella catarrhalis (6). The incidence of adverse reactions in the patients whose safety was evaluated was 15.7% (14/89), similar to that previously reported. The clinical efficacy of LVFX at the early phase, EOT and TOC of CAP, as assessed according to the new and former guidelines, was 70.4% (38/54) and 27.8% (15/54), 87.0% (60/69) and 79.1% (53/67), 87.5% (56/64) and 88.1% (59/67), respectively, with no significant differences. Therefore, the new efficacy evaluation method can be used in exchange for the former evaluation method.
- Published
- 2014
19. Significance of High Trough Concentration of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus Infection
- Author
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Issei Tokimatsu, Yuhki Sato, Kazufumi Hiramatsu, Hiroki Itoh, Jun-ichi Kadota, and Yosuke Suzuki
- Subjects
Pharmacology ,medicine.medical_specialty ,Teicoplanin ,business.industry ,General Medicine ,Staphylococcal infections ,medicine.disease ,medicine.disease_cause ,Loading dose ,Gastroenterology ,Methicillin-resistant Staphylococcus aureus ,Group B ,Cmin ,Infectious Diseases ,Oncology ,Staphylococcus aureus ,Internal medicine ,Drug Discovery ,medicine ,Pharmacology (medical) ,Trough Concentration ,business ,medicine.drug - Abstract
Background: Teicoplanin (TEIC) is a glycopeptide currently used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). A plasma trough concentration (Cmin) of >20 mg/l should be used for severe infections. The aim of this study was to assess the efficacy, safety and use of Cmin >20 mg/l on day 4-6 in patients with complicated MRSA infections. Methods: Blood samples were drawn from the 41 included patients just before TEIC administration between day 4 and 6. The patients were divided into three groups (group A: >20 mg/l, group B: 10-20 mg/l and group C: min on day 4-6. Results: Differences in efficacy between the groups were significant, but differences in safety were not. The patients in group A required lower cumulative doses than those in either groups B or C. Conclusions: The optimal clinical efficacy and safety might be associated with TEIC Cmin on the fourth to sixth day.
- Published
- 2014
20. Inhibitory effects of pitavastatin on fibrogenic mediator production by human lung fibroblasts
- Author
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Kazuhiko Hashinaga, Hisako Kushima, Kenji Umeki, Issei Tokimatsu, Hiroshi Ishii, Hiroaki Oka, Kazufumi Hiramatsu, Jun-ichi Kadota, Satoshi Toba, and Atsuko Iwata
- Subjects
Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Chemokine ,Cell signaling ,Statin ,medicine.drug_class ,Pulmonary Fibrosis ,Mevalonic Acid ,General Biochemistry, Genetics and Molecular Biology ,Transforming Growth Factor beta1 ,Mediator ,Fibrosis ,Internal medicine ,Pulmonary fibrosis ,medicine ,Humans ,Smad3 Protein ,Phosphorylation ,General Pharmacology, Toxicology and Pharmaceutics ,Pitavastatin ,Lung ,Cells, Cultured ,Dose-Response Relationship, Drug ,biology ,Interleukin-8 ,General Medicine ,Fibroblasts ,medicine.disease ,Endocrinology ,Quinolines ,biology.protein ,Cancer research ,Collagen ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Signal transduction ,Signal Transduction ,medicine.drug - Abstract
Aims Idiopathic pulmonary fibrosis continues to be a devastating clinical disorder for which there are few therapeutic options, and the pathogenesis of this disease remains largely unknown. Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in cholesterol biosynthesis, and they have been reported to exert pleiotropic effects on the cellular signaling involved in tissue inflammation and in organ fibrosis/remodeling. We examined the preventive effects of statins on fibrogenic mediator expression and production in normal human lung fibroblasts (NHLF). Main methods NHLF were pretreated with 100 nM pitavastatin or medium alone (control), and were then stimulated with transforming growth factor-β1 (TGF-β1). mRNA expression and protein secretion of several mediators from cells were analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay or multiplex assay. Key findings TGF-β1-induced expression or production of mediators, such as collagen-1, vascular endothelial growth factor and chemokine C–X–C motif ligand 8, in NHLF pretreated with pitavastatin was significantly suppressed with inhibition of Smad-3 phosphorylation, as compared to untreated controls. In addition, the inhibitory effects of pitavastatin were negated by addition of mevalonate. Significance Pitavastatin appeared to inhibit TGF-β1-induced fibrogenic mediator production from lung fibroblasts via the mevalonic cascade. Although further evaluation of the signaling pathways for these phenomena is necessary, our results suggest the potential benefits of pitavastatin.
- Published
- 2013
21. Association of sustained high plasma trough concentration of voriconazole with the incidence of hepatotoxicity
- Author
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Yosuke Suzuki, Kanako Kawasaki, Jun-ichi Kadota, Tomomi Goto, Yukie Sato, Hiroki Itoh, Issei Tokimatsu, Yuhki Sato, Kazuhiko Hashinaga, and Kazufumi Hiramatsu
- Subjects
Male ,medicine.medical_specialty ,Antifungal Agents ,Adolescent ,Clinical Biochemistry ,Pharmacology ,Trough (economics) ,Biochemistry ,Gastroenterology ,Liver Function Tests ,Pharmacokinetics ,Internal medicine ,medicine ,Humans ,Drug Dosage Calculations ,Trough Concentration ,Child ,Aged ,Aged, 80 and over ,Voriconazole ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,Biochemistry (medical) ,General Medicine ,Middle Aged ,Triazoles ,Logistic Models ,Pyrimidines ,Treatment Outcome ,Liver ,Mycoses ,Therapeutic drug monitoring ,Toxicity ,Female ,Drug Monitoring ,Liver function tests ,business ,medicine.drug - Abstract
Therapeutic drug monitoring (TDM) of voriconazole is important to optimize efficacy and to minimize toxicity and intolerance. In this study, we evaluated the effect of sustained high plasma trough concentration of voriconazole on the incidence of hepatotoxicity in hospitalized Japanese patients.Thirty-nine patients were divided into 3 groups according to trough concentrations in two consecutive TDMs:4 μg/ml in the first TDM (group A, n=25),4 μg/ml in the first and4 μg/ml in the second TDM (group B, n=8), and4 μg/ml in both first and second TDMs (group C, n=6).Incidences of hepatotoxicity in groups A, B and C were 16.0, 25.0 and 83.3%, and significant differences were observed between groups A and C and groups B and C. Multiple logistic regression analysis identified the classification into groups A, B and C as an independent variable of hepatotoxicity.These results suggest that sustained high trough concentration of voriconazole may increase the risk of hepatotoxicity, and decreasing trough concentration to4 μg/ml by dose adjustment after the initial TDM may reduce the incidence of hepatotoxicity in patients treated with voriconazole.
- Published
- 2013
22. Early switch therapy from intravenous sulbactam/ampicillin to oral garenoxacin in patients with community-acquired pneumonia: a multicenter, randomized study in Japan
- Author
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Futoshi Higa, Yoshihiro Yamamoto, Jiro Fujita, Katsunori Yanagihara, Issei Tokimatsu, Kazufumi Hiramatsu, Shigeru Kohno, Masao Tateyama, and Jun-ichi Kadota
- Subjects
Male ,Microbiology (medical) ,medicine.medical_specialty ,medicine.drug_class ,Antibiotics ,Administration, Oral ,Garenoxacin ,law.invention ,chemistry.chemical_compound ,Medical microbiology ,Japan ,Community-acquired pneumonia ,Randomized controlled trial ,Recurrence ,law ,Ampicillin ,Internal medicine ,Pneumonia, Bacterial ,medicine ,Humans ,Pharmacology (medical) ,Aged ,Aged, 80 and over ,business.industry ,Sulbactam ,Middle Aged ,medicine.disease ,Anti-Bacterial Agents ,Surgery ,Community-Acquired Infections ,Pneumonia ,Treatment Outcome ,Infectious Diseases ,chemistry ,Injections, Intravenous ,Female ,business ,Fluoroquinolones ,medicine.drug - Abstract
The switch from intravenous to oral antibiotic therapy is recommended for treating hospitalized patients with community-acquired pneumonia (CAP). We performed a multicenter, randomized study to assess the benefit of switching from intravenous sulbactam/ampicillin (SBT/ABPC) to oral garenoxacin (GRNX) in patients with CAP. Among adult CAP patients who must be hospitalized for intravenous antibiotic treatment, those with Pneumonia Patient Outcomes Research Team (PORT) scores of II–IV (mild to moderate) were initially treated with intravenous SBT/ABPC (6 g/day) for 3 days. A total of 108 patients who fulfilled the inclusion criteria (improved respiratory symptoms, CRP < 15 mg/dl, adequately improved oral intake, fever ≤ 38 °C for ≥ 12 h), were divided into two groups based on the antibiotic administered, the GRNX (switch to GRNX 400 mg/day) and SBT/ABPC groups (continuous administration of SBT/ABPC), for 4 days. Improvement in clinical symptoms, chest radiographic findings, and clinical effectiveness were evaluated by a central review board. Improvement in clinical symptoms was 96.3 and 90.2 % in the GRNX and SBT/ABPC groups, respectively. Improvement in chest radiographic findings was 94.4 and 90.2 % and clinical effectiveness was 94.4 and 90.2 % in the GRNX and SBT/ABPC groups, respectively. Microbiological efficacy was 90.9 and 69.2 % in the GRNX and SBT/ABPC groups, respectively. There were no significant differences between the groups. Converting to GRNX was as effective as continuous SBT/ABPC treatment in mild to moderate CAP patients in whom initial intravenous antibiotic treatment was successful.
- Published
- 2013
23. Inhibitory effect of statins on inflammatory cytokine production from human bronchial epithelial cells
- Author
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Issei Tokimatsu, Kenji Kishi, Hisako Kushima, Kazufumi Hiramatsu, Kenji Umeki, Atsuko Iwata, Kazuhiko Hashinaga, Hiroshi Ishii, Satoshi Otani, Ryo Shirai, and Jun-ichi Kadota
- Subjects
RHOA ,Statin ,Lipopolysaccharide ,medicine.drug_class ,medicine.medical_treatment ,Immunology ,Mevalonic Acid ,Bronchi ,Inflammation ,Respiratory Mucosa ,Cell Line ,chemistry.chemical_compound ,medicine ,Humans ,Immunology and Allergy ,cardiovascular diseases ,Pitavastatin ,Pravastatin ,biology ,nutritional and metabolic diseases ,Interleukin ,Epithelial Cells ,Original Articles ,Enzyme Activation ,Cytokine ,chemistry ,biology.protein ,Cytokines ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Inflammation Mediators ,medicine.symptom ,rhoA GTP-Binding Protein ,medicine.drug - Abstract
Summary Statins are 3-hydroxy-3-methylglutaryl-co-enzyme A reductase inhibitors of cholesterol biosynthesis, and have been reported to exert pleiotropic effects on cellular signalling and cellular functions involved in inflammation. Recent reports have demonstrated that previous statin therapy reduced the risk of pneumonia or increased survival in patients with community-acquired pneumonia. However, the precise mechanisms responsible for these effects are unclear. In the present study, we examined the effects of statins on cytokine production from lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B). Interleukin (IL)-6 and IL-8 mRNA expression and protein secretion in LPS-stimulated cells were inhibited significantly by the lipophilic statin pitavastatin and the hydrophilic statin pravastatin. As these inhibitory effects of statin were negated by adding mevalonate, the anti-inflammatory effects of statins appear to be exerted via the mevalonic cascade. In addition, the activation levels of Ras homologue gene family A (RhoA) in BEAS-2B cells cultured with pitavastatin were significantly lower than those without the statin. These results suggest that statins have anti-inflammatory effects by reducing cytokine production through inhibition of the mevalonic cascade followed by RhoA activation in the lung.
- Published
- 2012
24. Is Peak Concentration Needed in Therapeutic Drug Monitoring of Vancomycin? A Pharmacokinetic-Pharmacodynamic Analysis in Patients with Methicillin-Resistant Staphylococcus aureus Pneumonia
- Author
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Masaharu Takeyama, Yosuke Suzuki, Kanako Kawasaki, Issei Tokimatsu, Kazufumi Hiramatsu, Yuhki Sato, Hiroki Itoh, and Jun-ichi Kadota
- Subjects
Pharmacology ,Drug ,medicine.diagnostic_test ,business.industry ,media_common.quotation_subject ,Retrospective cohort study ,General Medicine ,medicine.disease_cause ,medicine.disease ,Methicillin-resistant Staphylococcus aureus ,Peak concentration ,Pneumonia ,Infectious Diseases ,Oncology ,Therapeutic drug monitoring ,Drug Discovery ,medicine ,Vancomycin ,Pharmacology (medical) ,In patient ,business ,medicine.drug ,media_common - Abstract
Background: We analyzed the pharmacokinetic-pharmacodynamic relationship of vancomycin to determine the drug exposure parameters that correlate with the efficacy and nephrotoxicity of vancomycin in patients with methicillin-resistant Staphylococcus aureus pneumonia and evaluated the need to use peak concentration in therapeutic drug monitoring (TDM). Methods: Serum drug concentrations of 31 hospitalized patients treated with vancomycin for methicillin-resistant S. aureus pneumonia were collected. Results: Significant differences in trough concentration (Cmin)/minimum inhibitory concentration (MIC) and area under the serum concentration-time curve (AUC0–24)/MIC were observed between the response and non-response groups. Significant differences in Cmin and AUC0–24 were observed between the nephrotoxicity and non-nephrotoxicity groups. Receiver operating characteristic curves revealed high predictive values of Cmin/MIC and AUC0–24/MIC for efficacy and of Cmin and AUC0–24 for safety of vancomycin. Conclusions: These results suggest little need to use peak concentration in vancomycin TDM because Cmin/MIC and Cmin are sufficient to predict the efficacy and safety of vancomycin.
- Published
- 2012
25. In vitro and in vivo potency of polymyxin B against IMP-type metallo-β-lactamase-producing Pseudomonas aeruginosa
- Author
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Yoshiko Miyajima, Kazufumi Hiramatsu, Eri Mizukami, Tetsunori Saikawa, Issei Tokimatsu, Kenji Kishi, Ryo Shirai, Ryotaro Morinaga, Jun-ichi Kadota, and Hiroshi Ishii
- Subjects
Male ,Microbiology (medical) ,Imipenem ,Colony Count, Microbial ,Bacteremia ,Microbial Sensitivity Tests ,Aztreonam ,Biology ,medicine.disease_cause ,beta-Lactamases ,Microbiology ,Mice ,Minimum inhibitory concentration ,chemistry.chemical_compound ,Drug Resistance, Bacterial ,polycyclic compounds ,medicine ,Animals ,Pseudomonas Infections ,Pharmacology (medical) ,Polymyxin B ,Antibacterial agent ,Cilastatin ,Colistin ,Reverse Transcriptase Polymerase Chain Reaction ,Pseudomonas aeruginosa ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,Survival Analysis ,Anti-Bacterial Agents ,Infectious Diseases ,chemistry ,medicine.drug - Abstract
Multidrug-resistant Pseudomonas aeruginosa, especially metallo-beta-lactamase (MBL)-producing P. aeruginosa, is an important pathogen in nosocomial infection and emergence of this pathogen has revived interest in polymyxin B (PMB) and colistin (COL). In this study, we evaluated the efficacies of PMB, COL and other antipseudomonal agents against IMP-type MBL-producing P. aeruginosa both in vitro and in vivo. A total of 75 isolates of bla(IMP)-positive P. aeruginosa obtained from clinical specimens (94.6% of isolates demonstrated resistance to beta-lactam, fluoroquinolone and aminoglycoside agents) were evaluated in the in vitro study. More than 90% of the examined isolates were susceptible to PMB (minimum inhibitory concentration for 50/90% of the isolates (MIC(50)/MIC(90)) 4/4 mg/L), although COL was less potent (MIC(50)/MIC(90) 8/16 mg/L). Cyclophosphamide-treated mice were intraperitoneally inoculated with bla(IMP)-positive P. aeruginosa. Treatment with PMB, but not COL, imipenem/cilastatin or aztreonam, significantly improved the survival rate and decreased the number of bacteria in the blood in a dose-dependent manner. Our results indicate that, among the agents studied, PMB is the most effective agent against bla(IMP)-positive P. aeruginosa.
- Published
- 2008
26. The prophylactic effectiveness of various antifungal agents against the progression of trichosporonosis fungemia to disseminated disease in a neutropenic mouse model
- Author
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Kenji Kishi, Hisako Kushima, Issei Tokimatsu, Minoru Ohama, Hiroshi Ishii, Jun-ichi Kadota, Kazufumi Hiramatsu, Kenji Umeki, and Kazuhiko Hashinaga
- Subjects
Male ,Microbiology (medical) ,medicine.medical_specialty ,Antifungal Agents ,Neutropenia ,Itraconazole ,Microbial Sensitivity Tests ,Biology ,Gastroenterology ,Mice ,Trichosporon ,Amphotericin B ,Internal medicine ,medicine ,Animals ,Pharmacology (medical) ,Antibiotic prophylaxis ,Cyclophosphamide ,Fluconazole ,Mycosis ,Fungemia ,Mice, Inbred ICR ,Animal Structures ,General Medicine ,Antibiotic Prophylaxis ,Trichosporonosis ,medicine.disease ,Survival Analysis ,Surgery ,Disease Models, Animal ,Treatment Outcome ,Infectious Diseases ,medicine.drug - Abstract
Neutropenic mice with latent trichosporonemia were given various antifungal agents (amphotericin B, fluconazole, itraconazole) or saline to determine which antifungal agent could be useful for prophylaxis. The 3-week-survival rate was 80% in the fluconazole group, 50% in the amphotericin B group, 45% in the itraconazole group, and 30% in the saline group. Compared with the other antifungal agents, fluconazole offered superior prophylaxis against the progression of trichosporonosis fungemia to disseminated disease (P
- Published
- 2007
27. Optimal vancomycin doses for methicillin-resistant Staphylococcus aureus infection in urological renal dysfunction patients
- Author
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Masato Fujisawa, Kazushi Tanaka, Issei Tokimatsu, Fukashi Yamamichi, Soichi Arakawa, Katsumi Shigemura, and Kayo Osawa
- Subjects
Nephrology ,Adult ,Male ,Methicillin-Resistant Staphylococcus aureus ,Urologic Diseases ,medicine.medical_specialty ,Adolescent ,Urology ,Renal function ,medicine.disease_cause ,Body weight ,Kidney ,Impaired renal function ,Young Adult ,Vancomycin ,Internal medicine ,medicine ,Humans ,Trough Concentration ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Middle Aged ,Staphylococcal Infections ,Methicillin-resistant Staphylococcus aureus ,Surgery ,Anti-Bacterial Agents ,Female ,Staphylococcus aureus infections ,business ,medicine.drug ,Glomerular Filtration Rate - Abstract
To investigate the optimal dose of vancomycin (VCM) for methicillin-resistant Staphylococcus aureus infections in the urological patients including renal dysfunction. We had 143 sets of available data from the consecutive patients treated in the urological department for analysis in VCM dose, VCM trough and estimated glomerular filtration rate: eGFR at VCM trough examination. Patients were classified according to eGFR level, and we calculated the regression line between VCM dose and VCM trough accordingly. Median VCM dose were 1000 (range 500–3500) mg per day, the VCM trough was 15.6 ± 7.89 μg/ml, and eGFR was 61.1 ± 27.2 ml/min/1.73 m2. Our regression analysis (x axis: VCM dose (mg) and y axis: VCM trough (μg/ml) was statistically significant in the group with eGFR of 30–60 ml/min/1.73 m2 (y = 26.103x + 481.7; r 2 = 0.1291) and the group with eGFR of 60–90 ml/min/1.73 m2 (y = 48.891x + 350.75; r 2 = 0.2561) in both with (p = 0.021 and 0.035, respectively) or without (p = 0.012 and 0.004, respectively) adjustments by body weight for VCM doses. These data showed that the optimal dose of VCM varied according to the eGFR value in consecutive urological patients with various renal functions.
- Published
- 2015
28. A case of empyema caused by Edwardsiella tarda
- Author
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Naoko Matsunaga, Hisako Kushima, Syunji Mizunoe, Tohru Yamasaki, Kazuhiko Hashinaga, Jun-ichi Kadota, and Issei Tokimatsu
- Subjects
Male ,Microbiology (medical) ,Pathology ,medicine.medical_specialty ,Pleural effusion ,medicine.medical_treatment ,Chest pain ,chemistry.chemical_compound ,Postoperative Complications ,Biopsy ,medicine ,Humans ,Edwardsiella tarda ,Empyema, Pleural ,Betamipron ,biology ,medicine.diagnostic_test ,business.industry ,Panipenem ,Liver Neoplasms ,Enterobacteriaceae Infections ,Middle Aged ,respiratory system ,biology.organism_classification ,medicine.disease ,Empyema ,respiratory tract diseases ,Pleural Effusion ,Radiography ,Infectious Diseases ,chemistry ,Drainage ,Hepatectomy ,medicine.symptom ,business ,medicine.drug - Abstract
In December 2003, a 57-year-old-man was diagnosed as having a hepatic tumor for which he had a hepatectomy. On pathology, the hepatic tumor biopsy specimen was diagnosed as malignant lymphoma. In February 2005, the patient was referred to our hospital because of fever and chest pain. A right pleural effusion was seen on chest X-ray. Microscopic examination of the stained pleural fluid revealed many neutrophils and Gram-negative rods, and Edwardsiella tarda was cultured from the pleural effusion fluid. These findings were consistent with an empyema caused by E. tarda. Therefore, we treated the patient with panipenem/betamipron and thoracic drainage. In this paper, we describe this rare case of empyema caused by E. tarda infection.
- Published
- 2006
29. Emerging Deep-seated Fungal Infection, Trichosporonosis
- Author
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Jun-ichi Kadota and Issei Tokimatsu
- Subjects
Male ,biology ,business.industry ,Opportunistic infection ,General Medicine ,Trichosporon asahii ,Middle Aged ,medicine.disease ,Trichosporonosis ,biology.organism_classification ,Communicable Diseases, Emerging ,Mycoses ,Trichosporon ,Amphotericin B ,Immunology ,medicine ,Humans ,Female ,business ,Pathogen ,Hypersensitivity pneumonitis ,Fungemia ,Aged ,medicine.drug - Abstract
Deep-seated trichosporonosis is a lethal opportunistic infection occasionally found in immunocompromised patients, particularly those who are neutropenic due to cytotoxic therapy for hematological malignancies. Trichosporon asahii is considered the principal etiologic agent of non-Candida fungemia and disseminated trichosporonosis in Japan. This infection may disseminate to multiple organs and difficult to diagnosis and treat. Because clinical findings and courses of trichosporonosis are similar to disseminated candidasis, it is impossible to distinguish these infections without fungal isolation. Monotherapy of amphotericin B is thought to be unsuccessful for this infection, and new antifungal agents echinocandins are also not active against Trichosporon species. Some clinical reports and animal models suggest that triazoles and combination therapies are most effective drugs against trichosporonosis. Recently, T. asahii isolates with reduced susceptibility in vitro to multi-antifungal agents are reported. T. asahii is the allergen of summer-type hypersensitivity pneumonitis and sometimes isolated from the houses environments, but it is not clear that the environmental strains directly infect to human. There is no clinical evidence that Trichosporon is the common outbreak pathogen in the hospital. However, it is necessary for a clinician to pay enough care as the lethal infections in immunocompromised patients.
- Published
- 2006
30. Antibiotic-induced apoptosis in human activated peripheral lymphocytes
- Author
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Kenji Kishi, Issei Tokimatsu, Jun-ichi Kadota, Syunji Mizunoe, Masaru Nasu, and Hiroyuki Nagai
- Subjects
Microbiology (medical) ,Programmed cell death ,medicine.drug_class ,Antibiotics ,Apoptosis ,Azithromycin ,Biology ,Lymphocyte Activation ,Macrolide Antibiotics ,Clarithromycin ,medicine ,Humans ,Pharmacology (medical) ,Lymphocytes ,Annexin A5 ,Biapenem ,Respiratory Tract Infections ,Antibacterial agent ,medicine.diagnostic_test ,General Medicine ,Anti-Bacterial Agents ,Infectious Diseases ,Bronchoalveolar lavage ,Immunology ,Macrolides ,Propidium ,medicine.drug - Abstract
Long-term administration of macrolide antibiotics reduced the number of lymphocytes in bronchoalveolar lavage fluid in patients with chronic airway inflammatory disease. To evaluate the inflammatory activity of macrolides, their effect on apoptosis of activated lymphocytes isolated from human peripheral blood was compared with that of other antibiotics. Macrolides, including clarithromycin and azithromycin, at a final concentration of 100 μg/ml accelerated apoptosis of activated lymphocytes, while other antibiotics such as fosfomycin sodium, β-lactams — ceftazidime, piperacillin sodium and biapenem, and a quinolone, ofloxacin, did not cause significant induction of apoptosis. Our results suggest that 14- or 15-membered ring macrolides are specifically involved in the augmentation of apoptosis of activated lymphocytes, and this may be of value therapeutically for chronic airway diseases.
- Published
- 2005
31. Pathogenesis of Trichosporon asahii and Strategies for Infectious Control of Disseminated Trichosporonosis
- Author
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Issei Tokimatsu, Jun-ichi Kadota, Reiko Karashima, Eiji Yamagata, Masaru Nasu, Hiroyuki Nagai, and Yuriko Yamakami
- Subjects
Male ,Antifungal Agents ,Opportunistic infection ,Trichosporon asahii ,Neutropenia ,Microbiology ,Mice ,Trichosporon ,Granulocyte Colony-Stimulating Factor ,medicine ,Animals ,Humans ,Blood culture ,Trichosporon mucoides ,Fluconazole ,Aged ,biology ,medicine.diagnostic_test ,business.industry ,Middle Aged ,Trichosporonosis ,medicine.disease ,biology.organism_classification ,Infectious Diseases ,Mycoses ,Immunology ,Drug Therapy, Combination ,Female ,business ,medicine.drug - Abstract
Deep-seated trichosporonosis is a lethal opportunistic infection in immunocompromised patients. Trichosporon asahii and T. mucoides are the most common strains of fungi that cause disseminated trichosporonosis. Thirteen patients were diagnosed with disseminated trichosporonosis over a 20 year period in Oita Medical University Hospital. The majority of them had underlying hematologic malignancies, for which they received cytotoxic chemotherapy resulting in neutropenia. For the rapid diagnosis of this condition, we developed a novel nested-PCR assay that detected DNA specific for Trichosporon asahii and Trichosporon mucoides in the serum of patients with the condition. In a retrospective study using these serum samples, the specific DNA fragment was detected a few days to a few weeks earlier than blood culture. To treat this infection, we studied the efficacy of granulocyte colony-stimulating factor (GCS-F) alone and in combination with antifungal agents against disseminated trichosporonosis in neutropenic mice. The results suggested that GCS-F might be a useful immunomodulator against Trichosporon infections in neutropenic mice and the therapeutic outcome improved when used in combination with fluconazole. Furthermore our experimental animal model demonstrated that disseminated trichosporonosis is induced by immunosuppresion in hosts with latent trichosporonemia which was detectable by the nested PCR but not by blood culture. We found that there is a critical period for the progression of disseminated trichosporonosis after entry of fungi into the bloodstream.
- Published
- 2003
32. A retrospective analysis to estimate target trough concentration of vancomycin for febrile neutropenia in patients with hematological malignancy
- Author
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Issei Tokimatsu, Kazuhiro Kohno, Yuhki Sato, Masao Ogata, Hiroki Itoh, Yosuke Suzuki, Yuko Morinaga, Kuniko Takano, Jun-ichi Kadota, and Kazufumi Hiramatsu
- Subjects
Adult ,Male ,medicine.medical_specialty ,Clinical Biochemistry ,Logistic regression ,Biochemistry ,Gastroenterology ,Nephrotoxicity ,Vancomycin ,Internal medicine ,medicine ,Humans ,Trough Concentration ,Aged ,Febrile Neutropenia ,Receiver operating characteristic ,medicine.diagnostic_test ,business.industry ,Biochemistry (medical) ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Logistic Models ,Treatment Outcome ,ROC Curve ,Therapeutic drug monitoring ,Hematologic Neoplasms ,Female ,Kidney Diseases ,Drug Monitoring ,business ,Febrile neutropenia ,Cohort study ,medicine.drug - Abstract
Background The target trough concentration of vancomycin in patients with febrile neutropenia has not been reported. The aim of this study was to estimate the target trough concentration for febrile neutropenia in patients with hematological malignancy. Methods In this retrospective, single-center, observational cohort study, 63 hospitalized patients with hematological malignancy who were treated with vancomycin for febrile neutropenia due to bacteriologically documented or presumptive Gram-positive infections were analyzed. Results A significant difference in the first trough concentration of vancomycin was observed between the response and non-response groups, and between the nephrotoxicity and non-nephrotoxicity groups. Multiple logistic regression analyses identified the first trough concentration as the only independent variable associated with clinical efficacy and nephrotoxicity of vancomycin. The areas under the ROC curves were 0.72 and 0.83 for clinical efficacy and nephrotoxicity, respectively. The cut-off values of the first trough concentration were 11.1 μg/ml for clinical efficacy (sensitivity 60%, specificity 87%) and 11.9 μg/ml for nephrotoxicity (sensitivity 77%, specificity 82%). Conclusions These results suggest a relationship of trough vancomycin concentration with clinical efficacy and incidence of nephrotoxicity. We propose a target trough vancomycin concentration of around 11.5 μg/ml for febrile neutropenia in patients with hematological malignancy.
- Published
- 2014
33. Clinical Characterization of blaIMP Positive Gram-negative Rods Isolated Cases
- Author
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Tetsunori Saikawa, Kazufumi Hiramatsu, Tetsuji Nakano, Issei Tokimatsu, Yuriko Yamakami, Junko Murakami, Masaru Nasu, Hiroyuki Nagai, Jun-ichi Kadota, Tohru Yamasaki, Eiji Yamagata, Tadao Nakano, Tomoku Ichimiya, and Norio Hirata
- Subjects
Imipenem ,biology ,business.industry ,medicine.drug_class ,Pseudomonas aeruginosa ,Urinary system ,Antibiotics ,General Medicine ,medicine.disease_cause ,biology.organism_classification ,beta-Lactamases ,Microbiology ,Multiple drug resistance ,Bacterial Proteins ,Gram-Negative Bacteria ,Genotype ,Serratia marcescens ,Pulsed-field gel electrophoresis ,Humans ,Medicine ,business ,medicine.drug - Abstract
We detected the metallo-beta-lactamase gene blaIMP positive strains of the gram-negative rods (GNR) isolated in Oita Medical University Hospital between 1993 and 1999 and studied the clinical characteristics of patients infected or colonized with blaIMP positive GNR. 25 strains (20 Pseudomonas aeruginosa and 5 Serratia marcescens) were detected and most of them were isolated from urinary samples after 1997. In the studies of antimicrobial susceptibility, some strains had sensitivity to aztreonum or imipenem although most of the strains showed multidrug resistance. When blaIMP positive GNR were isolated from patients, these strains were thought to have caused infection in 88% of the patients. About half of the patients were over 65 years old and had malignant diseases. Most of the patients had inserted urinary tract catheters, intratracheal tube or intravernous catheters. It was suggested that the insertion of the catheters were related to infection of blaIMP positive GNRs. Two patients were not treated with any antibiotics before the isolation of blaIMP positive GNRs although more than half of the patients were administered carbapenems and cephems. Most of strains were isolated in the same department and showed the same genotype by pulsed field gel electrophoresis.
- Published
- 2001
34. QUANTITATIVE PCR ASSAY USED TO MONITOR SERUM TRICHOSPORON ASAHII DNA CONCENTRATIONS IN DISSEMINATED TRICHOSPORONOSIS
- Author
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Kazuhiro Kogawa, Daisuke Kobayashi, Takashi Sugita, Shigeaki Nonoyama, Yoichiro Tsuji, Kohsuke Imai, Issei Tokimatsu, and Masatoshi Nozaki
- Subjects
Male ,Microbiology (medical) ,Antifungal Agents ,Antigens, Fungal ,Adolescent ,Graft vs Host Disease ,Microbial Sensitivity Tests ,Trichosporon asahii ,Polymerase Chain Reaction ,Microbiology ,law.invention ,Immunocompromised Host ,Trichosporon ,Antigen ,Polysaccharides ,law ,medicine ,Humans ,DNA, Fungal ,Polymerase chain reaction ,Bone Marrow Transplantation ,Voriconazole ,biology ,business.industry ,Fungi imperfecti ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Triazoles ,biology.organism_classification ,In vitro ,Latex fixation test ,Pyrimidines ,Infectious Diseases ,Real-time polymerase chain reaction ,Mycoses ,Pediatrics, Perinatology and Child Health ,business ,Latex Fixation Tests ,medicine.drug - Abstract
A bone marrow transplant recipient with disseminated trichosporonosis was successfully treated with voriconazole. Quantitative PCR assay results for Trichosporon asahii DNA in the sera were well correlated with the patient's clinical course. Based on the in vitro susceptibility test, the organism was susceptible to voriconazole.
- Published
- 2008
35. Exophiala dermatitidis pneumonia successfully treated with long-term itraconazole therapy
- Author
-
Katsuhiko Kamei, Takehiko Shigenaga, Issei Tokimatsu, Jun-ichi Kadota, Yutaka Mukai, Eishi Miyazaki, Shin-ichi Nureki, Masahiro Hata, and Kyoko Yarita
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Antifungal Agents ,Itraconazole ,Chest pain ,Bronchoscopy ,medicine ,Exophiala ,Humans ,Pharmacology (medical) ,Medical history ,Lung ,biology ,medicine.diagnostic_test ,business.industry ,Clinical course ,Pneumonia ,Middle Aged ,biology.organism_classification ,respiratory tract diseases ,Surgery ,Phaeohyphomycosis ,Infectious Diseases ,Bronchoalveolar lavage ,medicine.anatomical_structure ,Female ,medicine.symptom ,business ,Exophiala dermatitidis ,medicine.drug - Abstract
Exophiala dermatitidis pneumonia is extremely rare. Here we report a case of E. dermatitidis pneumonia successfully treated with long-term itraconazole therapy. A 63-year-old woman without a remarkable medical history developed a dry and chest pain. Chest radiographs revealed consolidation in the middle lobe of the lung. Cytologic examination by bronchoscopy showed filamentous fungi and E. dermatitidis was detected in the bronchoalveolar lavage fluid. After 5 months of itraconazole therapy, her symptoms improved and the area of consolidation diminished. Two weeks after discontinuing the itraconazole therapy, the area of consolidation reappeared. Itraconazole therapy was restarted and continued for 7 months. The abnormal shadow observed on the chest X-ray gradually diminished. Over a 27-month follow-up with periodic examination, there was no relapse and the patient had a favorable clinical course.
- Published
- 2013
36. A Randomized Controlled Study To Investigate The Safety And Pharmacokinetics Of Multiple Doses Of Ciprofloxacin Dry Powder For Inhalation In Japanese Patients With Moderate To Severe COPD
- Author
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Kazuhito Okumura, Issei Tokimatsu, Heino Stass, Yuki Suzaki, Kazufumi Hiramatsu, Takuya Morimoto, Hiromitsu Imai, and Jun-ichi Kadota
- Subjects
Moderate to severe ,COPD ,Inhalation ,business.industry ,Multiple dosing ,medicine.disease ,law.invention ,Ciprofloxacin ,Randomized controlled trial ,Pharmacokinetics ,Dry powder ,law ,Anesthesia ,Medicine ,business ,medicine.drug - Published
- 2012
37. Safety, Tolerability And Pharmacokinetics Of A Single Dose Of Ciprofloxacin Dry Powder For Inhalation In Japanese Patients With Mild To Moderate Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial
- Author
-
Kazufumi Hiramatsu, Heino Stass, Yuki Suzaki, Issei Tokimatsu, Hiromitsu Imai, Kazuhito Okumura, Jun-ichi Kadota, and Takuya Morimoto
- Subjects
Inhalation ,business.industry ,Pulmonary disease ,Safety tolerability ,law.invention ,Ciprofloxacin ,Randomized controlled trial ,Pharmacokinetics ,Dry powder ,law ,Anesthesia ,Medicine ,business ,medicine.drug - Published
- 2011
38. The Japanese Society of Internal Medicine
- Author
-
Futoshi Higa, Shigeru Kohno, Junichi Kadota, Katsunori Yanagihara, Kazufumi Hiramatsu, Jiro Fujita, Masao Tateyama, Koichi Izumikawa, and Issei Tokimatsu
- Subjects
Adult ,Male ,medicine.medical_specialty ,community-acquired pneumonia ,Haemophilus Infections ,macrolide resistance ,Drug resistance ,Azithromycin ,medicine.disease_cause ,Microbiology ,Hospitals, University ,Young Adult ,Community-acquired pneumonia ,Japan ,Internal medicine ,Drug Resistance, Multiple, Bacterial ,Streptococcus pneumoniae ,Drug Resistance, Bacterial ,Pneumonia, Mycoplasma ,Internal Medicine ,medicine ,Pneumonia, Bacterial ,Humans ,Adverse effect ,Aged ,Aged, 80 and over ,business.industry ,General Medicine ,Middle Aged ,Pneumonia, Pneumococcal ,medicine.disease ,Anti-Bacterial Agents ,Community-Acquired Infections ,Pneumonia ,Tolerability ,Female ,Macrolides ,business ,Empiric therapy ,medicine.drug - Abstract
Background and Objective The growing problem of drug resistance among respiratory pathogens in community-acquired pneumonia (CAP), particularly Streptococcus pneumoniae, (S. pneumoniae) has complicated initial empiric therapy of CAP. This study was undertaken to evaluate the efficacy and tolerability of a 3-day course of azithromycin in adults with mild to moderately severe CAP, and to determine whether in vitro macrolide resistance among strains of S. pneumoniae is related to clinical efficacy/failure. Methods An open-label, non-comparative study was undertaken at 3 university-affiliated hospitals in Japan. Patients were eligible if they were 18 years or older and had mild or moderately severe CAP. All patients received azithromycin 500 mg/day for three days, and clinical and microbiological responses were evaluated 1 and 2 weeks after initiating therapy. Results A total of 78 patients received the study medication, 59 of whom had sufficient data available for efficacy analysis. Overall, a good clinical response with azithromycin was achieved in 49 patients (83.1%) and a microbiological response was achieved in 78.3%. Azithromycin resistance, based on CLSI criteria, was demonstrated in 85.7% (12/14) of S. pneumoniae isolates, and the presence of ermB genes was found in 50.0% (7/14). However, among patients in whom S. pneumoniae was isolated (n=17), a good clinical response was achieved in 76.5% (13/17), and the microbiological response rate was 64.3% (9/14). Furthermore, 6 of 7 patients in whom high-level resistance was documented (MICs >256 μg/mL and carrying ermB genes) exhibited good clinical responses. Azithromycin was well tolerated; adverse events, mainly of a gastrointestinal nature, were recorded in 6 patients (7.7%). Conclusion Most patients responed well to azithromycin, indicating that azithromycin might be clinically effective for the treatment of CAP with macrolide-resistant S. pneumoniae. However, a larger study is necessary to prove the efficacy against macrolide-resistant S. pneumoniae., Internal Medicine, vol.48(7), pp.527-535; 2009
- Published
- 2009
39. Invasive pulmonary aspergillosis with hematological malignancy caused by Aspergillus terreus and in vitro susceptibility of A. terreus isolate to micafungin
- Author
-
Atsuko Iwata, Kazuhiro Kohno, Kenji Umeki, Kazufumi Hiramatsu, Kazuhiko Hashinaga, Hisako Kushima, Tetsunori Saikawa, Hiroshi Ishii, Kenji Kishi, Issei Tokimatsu, Jun-ichi Kadota, Minoru Ohama, and Masao Ogata
- Subjects
Adult ,Male ,Antifungal Agents ,Neutropenia ,Itraconazole ,Lipoproteins ,Opportunistic Infections ,Peptides, Cyclic ,Microbiology ,Minimum inhibitory concentration ,Echinocandins ,Lipopeptides ,Amphotericin B ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal Medicine ,Medicine ,Aspergillosis ,Humans ,Aspergillus terreus ,skin and connective tissue diseases ,biology ,Lung Diseases, Fungal ,business.industry ,Micafungin ,Sputum ,General Medicine ,bacterial infections and mycoses ,biology.organism_classification ,medicine.disease ,respiratory tract diseases ,Transplantation ,Leukemia ,Aspergillus ,Drug Therapy, Combination ,medicine.symptom ,business ,medicine.drug ,Stem Cell Transplantation - Abstract
A 35-year-old man developed invasive pulmonary aspergillosis (IPA) with severe neutropenia after umbilical cord stem cell transplantation for chronic myelogenous leukemia. Filamentous fungus isolated from his sputum was identified as Aspergillus terreus. Despite systemic amphotericin B (AMPH) administration, IPA progressed. However, intravenous administration of micafungin (MCFG) and oral itraconazole improved clinical data and symptoms, although he later died of massive hemoptysis. Examination of the in vitro susceptibility of this A. terreus isolate to MCFG revealed a good minimum inhibitory concentration and good time-kill assay results compared to AMPH. Thus, MCFG might be useful for IPA caused by A. terreus.
- Published
- 2007
40. [Efficacies and clinical roles of new antifungal agents]
- Author
-
Issei Tokimatsu and Jun-ichi Kadota
- Subjects
Antifungal Agents ,Echinocandin ,Lipoproteins ,Pharmacology ,Aspergillosis ,Microbiology ,Peptides, Cyclic ,chemistry.chemical_compound ,Echinocandins ,Lipopeptides ,Caspofungin ,Amphotericin B ,Medicine ,Humans ,Voriconazole ,Aspergillus ,biology ,business.industry ,Micafungin ,Triazoles ,bacterial infections and mycoses ,biology.organism_classification ,medicine.disease ,Infectious Diseases ,Pyrimidines ,chemistry ,business ,medicine.drug - Abstract
Micafungin, a new class of the antifungal agent "echinocandin" released in 2002, and voriconazole, a new triazole antifungal agent released in 2005 in Japan have in vitro activities against Aspergillus spp. Results of large-scale clinical trials in Europe and the United States showed voriconazole to have superior efficacy against invasive pulmonary aspergillosis in comparison with conventional amphotericin B, and caspofungin, a member of the echinocandins, was effective as an empirical antifungal therapy in patients with persistent fever and neutropenia. In this way, choices of therapeutic medicine for aspergillosis are increasing more and more, and it is expected that the method of treatment will change greatly in future. On the other hand, we need to establish a new standard therapy for aspergillosis to avoid the clinical disruption caused by the variety of pharmaceutical choice caused. In this report, we describe the role of new antifungal agents for non-fumigatus Aspergillus infections, and the breakthrough in counteracting fungal infection using these new drugs.
- Published
- 2006
41. Clarithromycin and azithromycin induce apoptosis of activated lymphocytes via down-regulation of Bcl-xL
- Author
-
Jun-ichi Kadota, Kenji Kishi, Masaru Nasu, Issei Tokimatsu, Hiroyuki Nagai, and Syunji Mizunoe
- Subjects
Adult ,Programmed cell death ,Fas Ligand Protein ,CD3 Complex ,Lymphocyte ,Immunology ,bcl-X Protein ,Antigen-Presenting Cells ,Down-Regulation ,Bcl-xL ,Apoptosis ,Biology ,Pharmacology ,Azithromycin ,In Vitro Techniques ,Lymphocyte Activation ,Fas ligand ,Bcl-2-associated X protein ,CD28 Antigens ,Clarithromycin ,medicine ,Immunology and Allergy ,Humans ,Lymphocytes ,fas Receptor ,Cells, Cultured ,Antibacterial agent ,bcl-2-Associated X Protein ,Membrane Glycoproteins ,Stimulation, Chemical ,Anti-Bacterial Agents ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-2 ,biology.protein ,medicine.drug - Abstract
To evaluate the anti-inflammatory action of macrolide antibiotics, we examined whether macrolide antibiotics could induce apoptosis of activated lymphocytes. The proportion of apoptotic cells was augmented by clarithromycin (CLR) and azithromycin (AZM) compared with control. There was no significant difference in Fas and Fas-ligand expression between the control and macrolide-treated groups. CLR and AZM inhibited the expression of Bcl-xL compared with that of control. Our results suggest that CLR and AZM enhance apoptosis of activated lymphocytes by down-regulation of Bcl-xL.
- Published
- 2004
42. Antimicrobial susceptibilities and analysis of genes related to penicillin or macrolide resistance in Streptococcus pneumoniae
- Author
-
Jun-ichi Kadota, Syunji Mizunoe, Kazufumi Hiramatsu, Yoshiko Mijajima, Masaru Nasu, Hiroyuki Nagai, Issei Tokimatsu, Tetsunori Saikawa, Kenji Kishi, and Minoru Ohama
- Subjects
Microbiology (medical) ,Penicillin Resistance ,Microbial Sensitivity Tests ,Penicillins ,medicine.disease_cause ,Benzylpenicillin ,Microbiology ,Bacterial Proteins ,Levofloxacin ,Streptococcus pneumoniae ,Drug Resistance, Bacterial ,medicine ,Humans ,Pharmacology (medical) ,Antibacterial agent ,biology ,Sputum ,Membrane Proteins ,General Medicine ,Pneumonia, Pneumococcal ,biology.organism_classification ,Streptococcaceae ,Antimicrobial ,Virology ,Anti-Bacterial Agents ,Penicillin ,Infectious Diseases ,Mutation ,Peptidyl Transferases ,Macrolides ,Bacteria ,medicine.drug - Abstract
One hundred and seventy-seven strains of Streptococcus pneumoniae derived from respiratory specimens between 1987 and 2001 were evaluated for their antimicrobial susceptibilities and distribution of genes related to penicillin and macrolide resistance. Resistance rates tended to be higher for the 1996–2001 isolates than for the 1987–1995 isolates for all β-lactams tested. For benzylpenicillin the MIC 90 value of the isolates derived between 1996 and 2001 was 1.56 mg/L, while that of strains isolated between 1987 and 1990 was 0.05 mg/L. Furthermore, the number of strains susceptible to macrolides also decreased, but only two strains isolated in 1993 were resistant to levofloxacin of the 177 S. pneumoniae strains tested. When of genes relating to penicillin resistance were analysed using PCR with primers specific to susceptible alleles, although more than 50% of strains from 1987 to 1990 and 1991 to 1995 revealed no mutations in the pbp 1a , 2x and 2b genes, only 30.0% of strains derived between 1996 and 2001 showed no mutations in the pbp gene. Strains having mutations in all three pbp genes ( 1a , 2x and 2b ) by the PCR method increased from only 2.2% in the 1987–1990 derived strains to 27.5% in the 1996–2001 strains. Furthermore, 64.1 and 60.0% of the isolates from 1987 to 1990 and 1991 to 1995, respectively, did not possess either the mefA or ermB by PCR analysis. Conversely, 75.0% of isolates from 1996 to 2001 possessed mefA and/or ermB . These genetic changes may explain the increase in the number of penicillin and macrolide resistant strains. We believe that it is important to evaluate changes in MIC as well as genetic mutations in order to select the most appropriate therapy for S. pneumoniae infections.
- Published
- 2003
43. Fungemia due toTrichosporon dermatisin a patient with refractory Burkitt's leukemia
- Author
-
Hiroe Kanamori, Masahiro Onozawa, Kaoru Kahata, Takashi Sugita, Rena Morita, Masahiro Asaka, Takeshi Kondo, Takahito Kawamura, Koji Akizawa, Shojiro Takahashi, Issei Tokimatsu, and Satoshi Hashino
- Subjects
Voriconazole ,medicine.medical_specialty ,business.industry ,Hematology ,Trichosporon dermatis ,bacterial infections and mycoses ,medicine.disease ,Dermatology ,Leukemia ,Refractory ,hemic and lymphatic diseases ,Rare case ,Medicine ,Burkitt s ,business ,Intensive care medicine ,Letter to the Editor ,Fungemia ,medicine.drug - Abstract
TO THE EDITOR: This is a rare case report of fungemia caused by Trichosporon dermatis in a patient with refractory Burkitt's leukemia who was administered prophylactic voriconazole.
- Published
- 2013
44. The Inhibitory Effects of Omalizumab on Allergic Inflammation in Patients With Severe Asthma
- Author
-
Hiroshi Ishii, Jun-ichi Kadota, Eiji Yamagata, Hisako Sonoda, Kenji Kishi, Kazufumi Hiramatsu, Ryo Shirai, Daisuke Yoshioka, Atsuko Iwata, Issei Tokimatsu, and Kazuhiko Hashinaga
- Subjects
Pulmonary and Respiratory Medicine ,business.industry ,Severe asthma ,Inflammation ,Omalizumab ,Critical Care and Intensive Care Medicine ,Inhibitory postsynaptic potential ,medicine.disease ,Allergic inflammation ,Immunology ,Medicine ,In patient ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug ,Asthma - Published
- 2011
45. Practice guidelines for therapeutic drug monitoring of voriconazole: a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring
- Author
-
Masao Kimura, Kei Kasahara, Issei Tokimatsu, Shunji Takakura, Masafumi Seki, Hiroshige Mikamo, Kenji Okada, Yukihiro Hamada, Yoshio Takesue, Yoshifumi Nishi, Masahiro Igarashi, Yusuke Tanigawara, Masahiro Kobayashi, Yoshiko Takahashi, Takahiro Mochizuki, Toshimi Kimura, Norio Ohmagari, and Kazuaki Matsumoto
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Antifungal Agents ,Consensus ,Cmax ,Guideline ,Therapeutic drug monitoring ,Japan ,Humans ,Medicine ,Arbekacin ,Pharmacology (medical) ,Intensive care medicine ,Voriconazole ,medicine.diagnostic_test ,business.industry ,Triazoles ,Clinical trial ,Regimen ,Pyrimidines ,Infectious Diseases ,Vancomycin ,Drug Monitoring ,business ,medicine.drug - Abstract
Arbekacin (ABK) was approved and widely used in Japan for treatment of patients infected with MRSA, and TDM was introduced in clinical practice. The Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring decided to develop a clinical practice guidelines for TDM of ABK for the following reasons. First, although the daily dose of 150e200 mg was approved in Japan, recent PK- PD studies revealed that higher serum concentration is required to achieve better clinical efficacy and several findings concerning the usefulness of higher dosage regimen have obtained recently. Second, although maximal concentrations that obtained immediately after the end of administration (Cmax )w as generally adopted, the serum concentration at 1 h after initiation of administration (peak serum con- centration (Cpeak)) proved to be more suitable as an efficacy indicator of aminoglycosides. Lastly, as ABK is approved only in Japan, no international practice guideline for TDM has not been available in ABK to date. This guideline evaluated the scientific data associated with serum ABK monitoring and provided rec- ommendations based on the available evidence. Potential limitations of this guideline, however, include the findings that few prospective clinical trials of TDM of ABK are available in the treatment of MRSA infections and that most of the published literature describes observational studies.
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